913
Views
61
CrossRef citations to date
0
Altmetric
REVIEWS

The Characteristics and Function of Bacterial Lipopolysaccharides and Their Endotoxic Potential in Humans

, &
Pages 189-218 | Accepted 20 Aug 2015, Published online: 25 Nov 2015

References

  • Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev 2007;90(3):859–904.
  • Hrncir T, Stepankova R, Kozakova H, et al. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMC Immunol 2008;9:65.
  • Trent MS, Stead CM, Tran AX, Hankins JV. Diversity of endotoxin and its impact on pathogenesis. J Endotoxin Res 2006;12(4):205–223.
  • Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56(7):1761–1772.
  • Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444(7121):860–867.
  • Lassenius MI, Pietiläinen KH, Kaartinen K, et al. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care 2011;34(8):1809–1815.
  • Page MG. The role of the outer membrane of Gram-negative bacteria in antibiotic resistance: Ajax’ shield or Achilles’ heel? Handb Exp Pharmacol 2012. p. 67–86.
  • Tran AX, Whitfield C. Lipopolysaccharides (Endotoxins). Encyclopedia of Microbiology. Third Edition ed. Oxford: Academic Press; 2009. p. 513–528.
  • Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev 2007;20(4):593–621.
  • Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002;71:635–700.
  • Raetz CR, Reynolds CM, Trent MS, Bishop RE. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 2007;76:295–329.
  • Munford RS, Varley AW. Shield as signal: lipopolysaccharides and the evolution of immunity to gram-negative bacteria. PLoS Pathog 2006;2(6):e67.
  • Matsuura M. Structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity. Front Immunol 2013;2013 May 24(4):109.
  • Lindberg AA, Weintraub A, Zähringer U, Rietschel ET. Structure-activity relationships in lipopolysaccharides of Bacteroides fragilis. Rev Infect Dis 1990;12(Suppl 2):S133–S141.
  • Brandenburg K, Schromm AB, Gutsmann T. Endotoxins: relationship between structure, function, and activity. Subcell Biochem 2010;53:53–67.
  • Martirosyan A, Ohne Y, Degos C, et al. Lipopolysaccharides with acylation defects potentiate TLR4 signaling and shape T cell responses. PloS One 2013;8(2):e55117.
  • Gutsmann T, Howe J, Zähringer U, et al. Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells. Innate Immun 2010;16(1):39–47.
  • Maitra U, Deng H, Glaros T, et al. Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide. J Immunol 2012;189(2):1014–1023.
  • Ohto U, Fukase K, Miyake K, Shimizu T. Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2. Proc Natl Acad Sci U S A 2012;109(19):7421–7426.
  • Abreu MT, Vora P, Faure E, et al. Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol 2001;167(3):1609–1616.
  • Furrie E, Macfarlane S, Thomson G, et al. Toll-like receptors-2, -3 and -4 expression patterns on human colon and their regulation by mucosal-associated bacteria. Immunology 2005;115(4):565–574.
  • Abreu MT, Arnold ET, Thomas LS, et al. TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells. J Biol Chem 2002;277(23):20431–20437.
  • Cario E, Podolsky DK. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000;68(12):7010–7017.
  • Park BS, Song DH, Kim HM, et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009;458(7242):1191–1195.
  • Hailman E, Lichenstein HS, Wurfel MM, et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 1994;179(1):269–277.
  • Gallay P, Barras C, Tobias PS, et al. Lipopolysaccharide (LPS)-binding protein in human serum determines the tumor necrosis factor response of monocytes to LPS. J Infect Dis 1994;170(5):1319–1322.
  • Wurfel MM, Kunitake ST, Lichenstein H, et al. Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med 1994;180(3):1025–1035.
  • Cekic C, Casella CR, Eaves CA, et al. Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A. J Biol Chem 2009;284(46):31982–31991.
  • Carpenter S, O'Neill LA. Recent insights into the structure of Toll-like receptors and post-translational modifications of their associated signalling proteins. Biochem J 2009;422(1):1–10.
  • Aksoy E, Taboubi S, Torres D, et al. The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nat Immunol 2012;13(11):1045–1054.
  • Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140(6):805–820.
  • Coats SR, Berezow AB, To TT, et al. The lipid A phosphate position determines differential host Toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria. Infect Immun 2011;79(1):203–210.
  • Zhang X, Morrison DC. Lipopolysaccharide-induced selective priming effects on tumor necrosis factor alpha and nitric oxide production in mouse peritoneal macrophages. J Exp Med 1993;177(2):511–516.
  • van ‘t Veer C, van den Pangaart PS, van Zoelen MA, et al. Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model. J Immunol 2007;179(10):7110–7120.
  • Draisma A, Pickkers P, Bouw MP, van der Hoeven JG. Development of endotoxin tolerance in humans in vivo. Crit Care Med 2009;37(4):1261–1267.
  • Hirohashi N, Morrison DC. Low-dose lipopolysaccharide (LPS) pretreatment of mouse macrophages modulates LPS-dependent interleukin-6 production in vitro. Infect Immun 1996;64(3):1011–1015.
  • Shnyra A, Brewington R, Alipio A, et al. Reprogramming of lipopolysaccharide-primed macrophages is controlled by a counterbalanced production of IL-10 and IL-12. J Immunol 1998;160(8):3729–3736.
  • Nomura F, Akashi S, Sakao Y, et al. Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol 2000;164:3476–3479.
  • Sly LM, Rauh MJ, Kalesnikoff J, et al. LPS-induced upregulation of SHIP is essential for endotoxin tolerance. Immunity 2004;21(2):227–239.
  • Suzuki M, Hisamatsu T, Podolsky DK. Gamma interferon augments the intracellular pathway for lipopolysaccharide (LPS) recognition in human intestinal epithelial cells through coordinated up-regulation of LPS uptake and expression of the intracellular Toll-like receptor 4-MD-2 complex. Infect Immun 2003;71(6):3503–3511.
  • del Fresno C, García-Rio F, Gómez-Piña V, et al. Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients. J Immunol 2009;182(10):6494–6507.
  • Bates JM, Akerlund J, Mittge E, Guillemin K. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2007;2(6):371–382.
  • Matsuura M, Kawasaki K, Kawahara K, Mitsuyama M. Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella enterica serovar Typhimurium having penta-acylated lipid A. Innate Immun 2012;18(5):764–773.
  • Matsuura M, Takahashi H, Watanabe H, et al. Immunomodulatory effects of Yersinia pestis lipopolysaccharides on human macrophages. Clin Vaccine Immunol 2010;17(1):49–55.
  • Audy J, Mathieu O, Belvis J, Tompkins TA. Transcriptomic response of immune signalling pathways in intestinal epithelial cells exposed to lipopolysaccharides, Gram-negative bacteria or potentially probiotic microbes. Benef Microbes 2012;3(4):273–286.
  • Zeuthen LH, Fink LN, Frokiaer H. Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta. Immunology 2008;123(2):197–208.
  • Lotz M, Gütle D, Walther S, et al. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med 2006;203(4):973–984.
  • Koyama I, Matsunaga T, Harada T, et al. Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. Clin Biochem 2002;35(6):455–461.
  • Lapaque N, Takeuchi O, Corrales F, et al. Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides. Cell Microbiol 2006;8(3): 401–413.
  • Shen H, Tesar BM, Walker WE, Goldstein DR. Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. J Immunol 2008;181(3):1849–1858.
  • Okemoto K, Kawasaki K, Hanada K, et al. A potent adjuvant monophosphoryl lipid A triggers various immune responses, but not secretion of IL-1beta or activation of caspase-1. J Immunol 2006;176(2):1203–1208.
  • Goto Y, Kiyono H. Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunological Reviews 2012;245(1):147–163.
  • Vamadevan AS, Fukata M, Arnold ET, et al. Regulation of Toll-like receptor 4-associated MD-2 in intestinal epithelial cells: a comprehensive analysis. Innate Immun 2010;16(2):93–103.
  • Palazzo M, Gariboldi S, Zanobbio L, et al. Cross-talk among Toll-like receptors and their ligands. Int Immunol 2008;20(5):709–718.
  • Otte JM, Cario E, Podolsky DK. Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology 2004;126(4):1054–1070.
  • Didierlaurent A, Brissoni B, Velin D, et al. Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide. Mol Cell Biol 2006;26(3):735–742.
  • Magalhaes JG, Tattoli I, Girardin SE. The intestinal epithelial barrier: How to distinguish between the microbial flora and pathogens. Semminars of Immunology 2007;19:106–115.
  • Mason KL, Huffnagle GB, Noverr MC, Kao JY. Overview of gut immunology. Advances in Experimental Medicine and Biology 2008;635:1–14.
  • Yanagibashi T, Hosono A, Oyama A, et al. Bacteroides induce higher IgA production than Lactobacillus by increasing activation-induced cytidine deaminase expression in B cells in murine Peyer's patches. Biosci Biotechnol Biochem 2009 Feb;73(2):372–377.
  • Chen KT, Malo MS, Moss AK, et al. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am J Physiol Gastrointest Liver Physiol 2010;299(2):G467–G475.
  • Mozes S, Lenhardt L, Martinková A. A quantitative histochemical study of alkaline phosphatase activity in isolated rat duodenal epithelial cells. Histochem J 1998;30(8):583–589.
  • Shifrin DA Jr, McConnell RE, Nambiar R, et al. Enterocyte microvillus-derived vesicles detoxify bacterial products and regulate epithelial-microbial interactions. Curr Biol 2012;22(7):627–631.
  • Sussman NL, Eliakim R, Rubin D, et al. Intestinal alkaline phosphatase is secreted bidirectionally from villous enterocytes. Am J Physiol 1989;257(1 Pt 1):G14–G23.
  • Kaur J, Madan S, Hamid A, et al. Intestinal alkaline phosphatase secretion in oil-fed rats. Dig Dis Sci 2007;52(3):665–670.
  • Goldberg RF, Austen WG Jr, Zhang X, et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A 2008;105(9):3551–3556.
  • Bentala H, Verweij WR, Huizinga-Van der Vlag A, et al. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock 2002;18(6):561–566.
  • Poelstra K, Bakker WW, Klok PA, et al. A physiologic function for alkaline phosphatase: endotoxin detoxification. Lab Invest 1997;76(3):319–327.
  • Poelstra K, Bakker WW, Klok PA, et al. Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am J Pathol 1997;151(4):1163–1169.
  • Chen KT, Malo MS, Beasley-Topliffe LK, et al. A role for intestinal alkaline phosphatase in the maintenance of local gut immunity. Dig Dis Sci 2011;56(4):1020–1027.
  • Vaishnava S, Hooper LV. Alkaline phosphatase: keeping the peace at the gut epithelial surface. Cell Host Microbe 2007;2(6):365–367.
  • Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 2007;86(5):1286–1282.
  • Schumann RR, Kirschning CJ, Unbehaun A, et al. The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. Mol Cell Biol 1996;16(7):3490–3503.
  • Harris HW, Grunfeld C, Feingold KR, Rapp JH. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. J Clin Invest 1990;86(3):696–702.
  • Mathison JC, Ulevitch RJ. The clearance, tissue distribution, and cellular localization of intravenously injected lipopolysaccharide in rabbits. J Immunol 1979;123(5):2133–2143.
  • Lamping N, Dettmer R, Schröder NW, et al. LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria. J Clin Invest 1998;101(10):2065–2071.
  • Levine DM, Parker TS, Donnelly TM, et al. In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci U S A 1993;90(24):12040–12044.
  • Parker TS, Levine DM, Chang JC, et al. Reconstituted high-density lipoprotein neutralizes gram-negative bacterial lipopolysaccharides in human whole blood. Infect Immun 1995;63(1):253–258.
  • Pajkrt D, Doran JE, Koster F, et al. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 1996;184(5):1601–1608.
  • Froon AH, Dentener MA, Greve JW, et al. Lipopolysaccharide toxicity-regulating proteins in bacteremia. J Infect Dis 1995;171(5):1250–1257.
  • Lu M, Munford RS. The transport and inactivation kinetics of bacterial lipopolysaccharide influence its immunological potency in vivo. J Immunol 2011;187(6):3314–3320.
  • Shao B, Lu M, Katz SC, et al. A host lipase detoxifies bacterial lipopolysaccharides in the liver and spleen. J Biol Chem 2007;282(18):13726–13735.
  • Erwin AL, Munford RS. Plasma lipopolysaccharide-deacylating activity (acyloxyacyl hydrolase) increases after lipopolysaccharide administration to rabbits. Lab Invest 1991;65(2):138–144.
  • Katz SS, Weinrauch Y, Munford RS, et al. Deacylation of lipopolysaccharide in whole Escherichia coli during destruction by cellular and extracellular components of a rabbit peritoneal inflammatory exudate. J Biol Chem 1999;274(51):36579–36584.
  • Munford RS, Hall CL. Uptake and deacylation of bacterial lipopolysaccharides by macrophages from normal and endotoxin-hyporesponsive mice. Infect Immun 1985;48(2):464–473.
  • Lu M, Zhang M, Takashima A, et al. Lipopolysaccharide deacylation by an endogenous lipase controls innate antibody responses to Gram-negative bacteria. Nat Immunol 2005;6(10):989–994.
  • Lu M, Varley AW, Ohta S, et al. Host inactivation of bacterial lipopolysaccharide prevents prolonged tolerance following gram-negative bacterial infection. Cell Host Microbe 2008;4(3):293–302.
  • Martin M, Katz J, Vogel SN, Michalek SM. Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. J Immunol 2001;167(9):5278–5285.
  • Medvedev AE, Lentschat A, Wahl LM, et al. Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. J Immunol 2002;169(9):5209–5216.
  • Li L, Cousart S, Hu J, McCall CE. Characterization of interleukin-1 receptor-associated kinase in normal and endotoxin-tolerant cells. J Biol Chem 2000;275(30):2340–2345.
  • Jacinto R, Hartung T, McCall C, Li L. Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance: distinct alterations in IL-1 receptor-associated kinase. J Immunol 2002;168(12):6136–6141.
  • Sato S, Takeuchi O, Fujita T, et al. A variety of microbial components induce tolerance to lipopolysaccharide by differentially affecting MyD88-dependent and -independent pathways. Int Immunol 2002;14(7):783–791.
  • Forestier C, Moreno E, Pizarro-Cerda J, Gorvel JP. Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. J Immunol 1999;162(11):6784–6791.
  • Burns K, Janssens S, Brissoni B, et al. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J Exp Med 2003;197(2):263–268.
  • Janssens S, Burns K, Tschopp J, Beyaert R. Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88. Curr Biol 2002;12(6):467–471.
  • Li CH, Wang JH, Redmond HP. Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation. J Leukoc Biol 2006;79(4):867–875.
  • Bagchi A, Herrup EA, Warren HS, et al. MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists. J Immunol 2007;178(2):1164–1171.
  • Landoni VI, Chiarella P, Martire-Greco D, et al. Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice. Clin Exp Immunol 2012;168(1):153–163.
  • Li P, Allen H, Banerjee S, et al. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 1995;80(3):401–411.
  • Chilton PM, Embry CA, Mitchell TC. Effects of differences in lipid a structure on TLR4 pro-inflammatory signaling and inflammasome activation. Front Immunol 2012;3:154.
  • Thompson BS, Chilton PM, Ward JR, et al. The low-toxicity versions of LPS, MPL adjuvant and RC529, are efficient adjuvants for CD4+ T cells. J Leukoc Biol 2005;78(6):1273–1280.
  • Blomkalns AL, Stoll LL, Shaheen W, et al. Low level bacterial endotoxin activates two distinct signaling pathways in human peripheral blood mononuclear cells. J Inflamm (Lond) 2011;8(4).
  • Holven KB, Retterstøl K, Ueland T, et al. Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype. PloS One 2013;8(11):e78241.
  • Mehta NN, McGillicuddy FC, Anderson PD, et al. Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes 2010;59(1):172–181.
  • Pussinen PJ, Havulinna AS, Lehto M, et al. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care 2011;34(2):392–397.
  • Kaliannan K, Hamarneh SR, Economopoulos KP, et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci U S A 2013;110(17):7003–7008.
  • Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007;50(11):2374–2383.
  • Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009;58(8):1091–1103.
  • Amar J, Burcelin R, Ruidavets JB, et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 2008;87(2):1219–1223.
  • Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 2010;33(5):991–997.
  • Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 2009;32(12):2281–2287.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.